HES5

Chr 1

hes family bHLH transcription factor 5

Also known as: bHLHb38

NCBI Gene: 388585ENSG00000197921UniProt: Q5TA89

This gene encodes a member of a family of basic helix-loop-helix transcriptional repressors. The protein product of this gene, which is activated downstream of the Notch pathway, regulates cell differentiation in multiple tissues. Disruptions in the normal expression of this gene have been associated with developmental diseases and cancer. [provided by RefSeq, Dec 2008]

Research Assistant →
0
Active trials
17
Pubs (1 yr)
0
P/LP submissions
—
P/LP missense
1.34
LOEUF
DN
Mechanism· predicted
Clinical Summary— HES5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.34LOEUF
pLI 0.249
Z-score 1.20
OE 0.30 (0.10–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.59Z-score
OE missense 1.27 (1.01–1.61)
49 obs / 38.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.30 (0.10–1.34)
0≤0.351.4
Missense OE1.27 (1.01–1.61)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 1 / 3.4Missense obs/exp: 49 / 38.6Syn Z: -0.55
DN
0.6355th %ile
GOF
0.4481th %ile
LOF
0.48top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HES5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Salidroside targets the Notch1/Hes5 axis to reconstruct the molecular innate immune-vascular network and correlates with repair after ischemic stroke.
Zeng J et al.·Front Immunol
2026Open Access
Low SVEP1 in intrahepatic cholangiocarcinoma mediates phenotype switching-driven metastasis by Jag2/Notch1/Hes5.
Chen L et al.·Cell Death Dis
2025Open Access
PCSK9 Loss-of-Function Disrupts Cellular Microfilament Network via LIN28A/HES5/JMY Axis in Neural Tube Defects.
Li X et al.·Adv Sci (Weinh)
2025Open Access
Androgen receptor inhibitor ameliorates pulmonary arterial hypertension by enhancing the apoptosis level through suppressing the Notch3/Hes5 pathway.
Sun J et al.·Front Pharmacol
2025Open Access
Hes5+ astrocytes potentiate primary afferent Aδ and C fiber-mediated excitatory synaptic transmission to spinal lamina I neurons.
Kagiyama I et al.·Mol Brain
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients